Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 31 patients with malignant pleural mesothelioma disease, limited to one hemithorax, were entered into a phase II study of surgery and intracavitary photodynamic therapy. Photofrin, 2 mg/kg, was injected intravenously, and 48 hours later the patient was taken to the operating room. Bulk tumor was excised by a pleuropneumonectomy or pleurectomy. The patient then received 20-25 J/cm2 of 630 nm light energy from an argon dye laser. The overall estimated median survival of patients of all stages was 12 months. Survival of stage III and stage IV patients was 8 months. The median survival of 9 patients with stage I and II disease was 21 months. We plan to continue this clinical trial; however, entry will be limited to patients with stage I and II disease. The light dose for photodynamic therapy will be carefully increased to find the maximal tolerated dose.
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PMID:Intracavitary photodynamic therapy for malignant pleural mesothelioma. 756 59

Photofrin (25 mg/kg) was administered to the FsaR fibrosarcoma-bearing mice (either syngeneic or severe combined immunodeficient [SCID]) and the tumors were excised 24 h later. The photosensitizer content in the cells dissociated from tumor tissue was analyzed using flow cytometry. Staining the cell suspensions with the monoclonal antibodies against specific membrane markers served to identify the malignant cells and various types of host immune cells infiltrating the tumor. Photofrin content was also examined in the cells from normal tissues of the tumor-bearing mice (spleen, heart muscle, peritoneal macrophages). The results show a marked heterogeneity in the Photofrin cellular content of FsaR tumor, particularly within the population of tumor-associated macrophages (TAM). The Photofrin levels in some TAM were lower or similar to those in the malignant cells. In contrast, a subpopulation of TAM accumulated very high levels of the photosensitizer, which exceeded by far the levels found in the other tumor cell populations. This TAM fraction was characterized by particularly high expression of interleukin-2 receptors and increased cell size and granularity when compared to the other TAM, which suggests that these macrophages are in the activated state. Their average Photofrin content was almost 13 times higher than in the malignant cells. The lowest photosensitizer levels in the tumor were found in tumor-infiltrating leukocytes other than TAM. In FsaR tumors growing in SCID mice, the pattern of Photofrin distribution in TAM and other cellular populations was similar to that found in tumors growing in syngeneic mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Photofrin accumulation in malignant and host cell populations of a murine fibrosarcoma. 763 61

For evaluating the role of photodynamic therapy (PDT) in the local treatment of acquired immune deficiency syndrome (AIDS)-related cutaneous Kaposi's sarcoma (KS), nine treatments were performed in eight human immunodeficiency virus-positive homosexual men. The patients received 2 mg Photofrin/kg and either 120 J/cm2 (n = 5) or 70 J/cm2 (n = 4) laser light (630 nm). A total of 83 lesions were evaluable for response with a follow-up of 3-8 months. The overall response rates by patient for all treated lesions were 50-100% (120 J/cm2) and 83.3-90.3% (70 J/cm2), with a median duration of 3 months (range, 2-6 months). Tumors located at the head had higher response rates than those at the trunk or extremities (p = 0.005 and p - 0.015 respectively). The size of the KS showed a negative relationship with the probability of complete response (p = 0.047). Local and general side effects occurred, including pain, blisters, temperature increase, muscle stiffness, and severe edema. The cosmetic result was unsatisfactory because of a high prevalence of scars and long-lasting hyperpigmentation. Although the response rates of PDT are high, light dose of 70-120 J/cm2 cannot be recommended in the treatment of cutaneous KS in combination with 2 mg/kg Photofrin because of severe side effects and unsatisfactory cosmetic result.
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PMID:Photodynamic therapy in AIDS-related cutaneous Kaposi's sarcoma. 764 86

Porfimer sodium (Photofrin II) is a photosensitizer which distributes selectively to tumor tissues, and causes tumor cell death by combination with light irradiation. Photodynamic therapy (PDT) by combination of porfimer sodium and laser was developed as a new cancer therapy. Tumor selectivity of porfimer sodium are based on the following reasons; 1) high affinity for lipoprotein, especially, low density lipoprotein (LDL), 2) elevation of LDL receptor activity in cancer tissue, and 3) lack or imcompleteness of lymphatic system in cancer tissue. Porfimer sodium is activated by laser irradiation at 630 nm, which can reacts with tissue oxygen to produce highly reactive excited siglet oxygen (1O2). This highly reactive molecule is subsequently capable of killing tumor cells through oxidation of cellular component like mitochondrial enzymes. In addition, this highly reactive intermediate causes destruction of the tumor capillaries, which accelerates tumor cell death. The growth suppression or lethal damage to tumor cells by PDT of porfimer sodium and excimer dye laser were observed in experimental tumor models. In human clinical trials, the rates of complete response (CR) for roentgenographically occult lung cancer, stage I lung cancer, superficial esophageal cancer, superficial gastric cancer and carcinoma in situ or dysplasia of the cervix were 84.8%, 50.0%, 90.0%, 87.5% and 94.4%, respectively. The major side effects were cutaneous symptoms e.g. photosensitivity, pigmentation, increasing GOT, GPT but these symptoms were not severe. PDT using porfimer sodium and excimer dye laser must be clinically useful for the treatment of inoperable early cancer or conservation of organ functions.
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PMID:[Porfimer sodium (Photofrin-II)]. 766 80

We examined the effectiveness of systemic administration of delta-aminolevulinic acid (delta-ALA) to induce endogenous protoporphyrin as a regimen for use in photodynamic therapy (PDT) of transplanted R3230AC rat mammary adenocarcinomas in vivo. Levels of porphyrins synthesized in various tissues after systemic administration of delta-ALA differed, with their accumulation in tumor tissue being dependent on both the dose and the time after delta-ALA administration. Tumor, liver, and intestine contained greater than 3.0 micrograms porphyrin/g tissue at 3 h after delta-ALA injection, whereas porphyrin levels in rat skin and muscle at that time were an order of magnitude lower. Analysis of tissue by HPLC revealed that the predominant porphyrin synthesized in tumors was protoporphyrin IX, whereas in liver, 18% of the total porphyrin detected was protoporphyrin IX, and in muscle, it was undetectable. Time-dependent studies of the uptake of 14C label from delta-ALA into the various tissues were not predictive of either the total amount of porphyrin or which porphyrin species would be present at 3 h after delta-ALA injection. Additionally, no simple relationship was apparent between the activities of certain selected enzymes involved in heme biosynthesis and the concentrations of porphyrins in the different tissues. High levels of tumor protoporphyrin IX were sustained by administration of two sequential doses of delta-ALA, at 3.0 and 1.5 h prior to irradiation. Using these treatment conditions, we inhibited R3230AC growth to an extent that was comparable to that obtained for Photofrin-induced PDT. High energy phosphate metabolism, measured by nuclear magnetic resonance spectroscopy in vivo, was dramatically impaired after delta-ALA-based PDT, with tumor ATP levels reduced to near zero by 4 h after irradiation. Our results demonstrated that delta-ALA-based PDT may be an alternative to current treatment protocols that use exogenously administered photosensitizers.
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PMID:Effectiveness of delta-aminolevulinic acid-induced protoporphyrin as a photosensitizer for photodynamic therapy in vivo. 771 81

A body of indirect evidence has suggested the involvement of reactive oxygen species (ROS) in tumor promotion. However, direct evidence for the involvement of in situ generated ROS in tumor promotion is lacking at present. This study provides the first in situ evidence for the involvement of ROS in stage I tumor promotion. Earlier we have shown that parenteral administration of Photofrin-II (a mixture of porphyrins) to mice followed by their exposure to visible light generates ROS. In this study we further provide E.S.R. spectral evidence that both O2.- and .OH radicals are generated during tissue photosensitization. The free radicals/ROS generation is followed by the development of cutaneous inflammation which is maximum at six hours after photosensitization and develops in a dose dependent manner. The epidermal myeloperoxidase activity which represents neutrophil infiltration is also increased more than 160% of the control value. The histopathology of skin tissues of 7,12 dimethyl benz(a)anthracene initiated mice receiving multiple treatments of Pf-II and light for a period of four weeks indicates pronounced epidermal hyperplasia, glandular hyperplasia, dark basal keratinocytes induction characterized by the high uptake of the dye and frequent neutrophil infiltrations. Our data indicate that ROS generated in situ as a result of porphyrin-mediated cutaneous photosensitization results in the development of changes characteristic of stage I tumor promotion in murine skin.
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PMID:Evidence that in situ generated reactive oxygen species act as a potent stage I tumor promoter in mouse skin. 773 40

Photodynamic therapy has demonstrated efficacy toward primary, metastatic and recurrent human tumors. Here, we investigated the ability of photodynamic therapy, using Photofrin, to inhibit growth of R3230AC mammary adenocarcinomas when tumors were treated as original implants and again as lesions recurring at the initial treatment site. The results demonstrate that both initial implants and lesions recurring after the first photodynamic treatment respond similarly to the same photodynamic therapy protocol, with mean tumor volume doubling times of approximately 11 days in both cases. Cells cultured from original tumor implants or tumors that recurred after photodynamic treatment accumulate equivalent amounts of [14C]polyhematoporphyrin. Single cell suspensions prepared from either original or recurrent tumors from animals administered 5 mg/kg Photofrin and exposed to light in vitro displayed comparable phototoxicity. Additionally, examination of tumors by light microscopy revealed no morphological differences between the original tumor implants and the recurrent lesions. Taken together, these data indicate that lesions which recurred at the site of the initial photodynamic treatment were not resistant to a second identical course of photodynamic therapy.
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PMID:Efficacy of photodynamic therapy on original and recurrent rat mammary tumors. 789 8

From April 1991 to May 1993, 23 patients entered a phase II clinical study of surgical resection and adjuvant intracavitary photodynamic therapy for malignant pleural mesothelioma. Two days preoperatively, patients received an intravenous injection of 2 mg/kg of the photosensitizer Photofrin. Six patients underwent a pleuro-pneumonectomy, and 15 patients a pleurectomy, after which intracavitary photodynamic therapy was administered. A total light energy dose of 20 to 25 J/cm2 was given. In 2 patients the tumor was unresectable due to intrapericardial invasion. Postoperative complications were noted in more than 50 percent of patients; 2 patients died of postoperative complications. Postoperative survival was analyzed according to intraoperative staging proposed by the American Joint Committee for Cancer Staging, published in 1992. The overall estimated median survival is 12 months; that of stage III and IV patients is 7 months. Five patients with stage I and II diseases (who had grossly complete resection by pleurectomy) are alive, disease-free, for 11, 17, 18, 21, and 33 postoperative months. Intraoperative staging is important in carrying out further clinical studies of malignant pleural mesothelioma.
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PMID:Operation and intracavitary photodynamic therapy for malignant pleural mesothelioma: a phase II study. 794 21

Photodynamic therapy (PDT) has been used investigationally for the treatment of lung cancer since 1980. Following systemic administration of a photosensitizing agent such as porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada), specialized optical delivery systems are engaged to deliver light of a specific wavelength (630 nm for porfimer sodium) to neoplastic tissue. A promising use of PDT appears to be treatment of early stage lung carcinoma. Phase I-II clinical trials by Hayata's group in Japan showed that for superficial early lung cancer less than 1 cm in surface diameter, complete eradication can be achieved in approximately 90% of cases. Additional phase II-III clinical trials have demonstrated an average of 90% complete response rates for superficial tumors less than 1 cm in diameter. Preoperative PDT may be useful for larger neoplasms to reduce tumor burden and potentially lessen the degree of surgery required. At the British Columbia Cancer Agency, 22 patients with 30 radiologically occult cancers were treated with PDT. In contrast to Hayata's studies, most of these patients had rather extensive tumor burden. Thirty percent of the tumors involved two or more bronchi, and more than half of them were greater than 1 cm in surface diameter. Twenty-three percent of the cases were bronchial stump recurrences. In the group of patients with bronchial stump recurrence, although a complete response was obtained with PDT initially, local recurrences occurred in 75% of cases. These results suggest that recurrent tumor in the bronchial stump should not be treated with PDT because of difficulty in delivering light endobronchially to distal tissues. Photodynamic therapy may have a role in the palliation of advanced, inoperable, obstructive bronchial tumors. Phytodynamic therapy in combination with external radiotherapy may produce better local control than external radiotherapy alone in patients with obstructive bronchial cancers. Photodynamic therapy and conventional Nd:YAG laser therapy appear to be equally effective in relieving intraluminal obstruction by tumor. An advantage of PDT for this purpose is longer time to treatment failure; a disadvantage is photosensitization that usually occurs for up to 4 weeks after treatment. In summary, PDT is a promising curative treatment for patients with small early bronchial cancers.
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PMID:Photodynamic therapy of lung cancer. 799 2

Esophageal carcinoma usually is diagnosed at an advanced, incurable stage. In patients with good operative risk, surgery is still considered the ideal treatment. Patients with coexisting major medical conditions in whom resective surgery is precluded may benefit from several therapeutic options, including photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada), dilation, thermal destruction, Nd:YAG laser ablation, injection therapy, and placement of prosthetic tubes. Photodynamic therapy with porfimer sodium is thought to have a direct toxic effect on malignant cells via the production of singlet oxygen, which damages the microvasculature of the tumor and renders it ischemic. The 630 nm wavelength used for clinical PDT exhibits the greatest relative degree of light penetration into tissue, with corresponding activation of retained photosensitizer. The efficacy of PDT with porfimer sodium is closely related to stage of disease. It should be emphasized that PDT has been shown to be potentially curative in patients with early, noninvasive tumors of both squamous and glandular (adenocarcinoma) histologies. Eighty-three patients with esophageal carcinoma were treated using PDT. At presentation, 60% of patients had recurrence following previous radiotherapy or chemotherapy. Patients with less advanced disease had a better response to PDT with regard to relief of dysphagia and prolongation of survival. Photodynamic therapy was found to be more useful than Nd:YAG laser therapy for high, upper third lesions, especially circumferential ones. For tumors larger than 8 cm, PDT was twice as effective as Nd:YAG laser therapy in establishing prolonged lumen patency, especially for adenocarcinomas. Photodynamic therapy appears to have the added advantages of fewer treatments and less pain. The role of PDT in gastrointestinal malignancies continues to evolve.
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PMID:Photodynamic therapy and cancer of the esophagus. 799 3


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